Mitochondrial dysfunction and oxidative stress damage are hallmarks of osteoarthritis (OA). Mesenchymal stem cell (MSC)-derived exosomes are important in intercellular mitochondria communication. However, the use of MSC exosomes for regulating mitochondrial function in OA has not been reported. This study aimed to explore the therapeutic effect of MSC exosomes in a three dimensional (3D) printed scaffold for early OA therapeutics. Methods : We first examined the mitochondria-related proteins in normal and OA human cartilage samples and investigated whether MSC exosomes could enhance mitochondrial biogenesis in vitro . We subsequently designed a bio-scaffold for MSC exosomes delivery and fabricated a 3D printed cartilage extracellular matrix (ECM)/gelatin methacrylate (GelMA)/exosome scaffold with radially oriented channels using desktop-stereolithography technology. Finally, the osteochondral defect repair capacity of the 3D printed scaffold was assessed using a rabbit model. Results : The ECM/GelMA/exosome scaffold effectively restored chondrocyte mitochondrial dysfunction, enhanced chondrocyte migration, and polarized the synovial macrophage response toward an M2 phenotype. The 3D printed scaffold significantly facilitated the cartilage regeneration in the animal model. Conclusion : This study demonstrated that the 3D printed, radially oriented ECM/GelMA/exosome scaffold could be a promising strategy for early OA treatment.

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A series of Ce(1-x)M(x)O(2-δ) (M = Gd, Zr, La, Sm, Y, Lu, and Pr) samples were characterized by Raman spectroscopy to investigate the evolution of defect sites (oxygen vacancies and MO(8)-type complex) and their distributions in the samples. It was found that the evolution of oxygen vacancies was due to the different ionic valence state of dopant from that of Ce(4+), while the evolution of the MO(8)-type complex was due to the different ionic radius of dopant from that of Ce(4+). The distributions of defect sites were investigated using 325 and 514 nm excitation laser lines, indicating that the defect sites were surface enriched. Moreover, the increasing ordering level of the sample led to a decline in the concentration of the MO(8)-type complex in the sample but the constant concentration of oxygen vacancies, implying that the metastable MO(8)-type complex species were more disordered compared to the oxygen vacancies.